This application requests funding for an integrated system that incorporates the following components: a micromanipulation- microinjection apparatus, and inverted microscope with phase contrast, epi-fluorescence and Namarski DIC optics and a CCD camera with an image processing system. At present, there is neither a system of comparable capability at Fox Chase Cancer (FCCC) nor is there available funding for such instrumentation. The research interests of the 11 NIH funded investigators who will be the major users of the requested instrumentation vary widely. However, their research efforts all converge in the detailed analysis of cultured cells at the microscopic level. Acquisition of the requested system will permit an extension of each investigator research from analysis of cell populations to the level of single cells. The various components of the requested system were chosen based on the diversity of this research interest, with the goal of satisfying the investigators~ immediate, as well as long term needs. The ultimate goal of all of the research programs described in this application is to understand human disease processes. This will be accomplished through study of the regulation of cell morphology and growth by tumor suppressors, oncogenes, signal transduction molecules, viruses and modifiers of cell polarity. Many of the cellular effectors which will be investigated in these studies have already been identified through analysis of mutations in a variety of malignant states in humans. Some of the proposed experiments describe analysis of hepatitis delta and hepatitis B viral replication, which may ultimately aid in the treatment of hepatitis, a disease that is associated with significant morbidity in humans and represents the leading cause of hepatocellular carcinoma. Others involve analysis of retroviral systems of relevance to cancer and AIDS. All of these projects share a common need for high-resolution optics, micromanipulation and microscope image processing capabilities, a requirement that can be served most effectively by access to the requested system. The requested system will be housed, operated and technically supported in the Cell Culture Facility a FCCC. The shared Facility is an ideal location for the integrated system as it serves the majority of NIH funded laboratories at FCCC and is a hub of collaborative efforts with outstanding, highly trained technical support.